The overall goal of this study is to investigate the relationship between endocrine disrupting chemicals (EDCs), specifically select phthalates and persistent organochlorine pesticides (OCPs), and risk of endometriosis in reproductive-age women. There is emerging concern about the safety of phthalates, man-made chemicals used in the manufacturing of many household items including plastics and personal care products. Nearly ubiquitous detection of several phthalate metabolites in the US population suggests widespread exposure. Similarly concerning, OCPs are pesticides that continue to persist in the environment despite being banned or restricted in use over the past several decades. Both phthalates and OCPs are EDCs that mimic or alter endogenous hormone activity, however, little data exists about the potential adult human health effects posed by these EDCs. This study will address this gap in knowledge by investigating the impact of adult exposure to phthalates and OCPs in relation to a prevalent female reproductive condition. Endometriosis, characterized by the implantation of endometrial tissue outside the uterus, affects approximately 8-10% of reproductive age women in the US and is associated with severe pelvic pain and infertility. The central hypothesis in this study is that exposure to phthalates or OCPs during the menstrual cycle results in structural changes in hormonally- responsive endometrial tissue that alter the dynamic regulation of tissue proliferation and breakdown and thus increase the risk of endometriosis. To test this hypothesis, a population-based case-control study will be conducted among women ages 18-49 who are enrollees of a large, mixed-model health care system in Washington State using archived biosamples and data collected in the "Women's Risk of Endometriosis" study and continuation study of recurrence (R01 HD33792) and the "Persistent Organic Pollutants and Endometriosis Risk" ancillary study (EPA grant no. R829438). The study will analyze archived urine specimens from 135 cases and 165 controls for phthalate metabolite levels and will use data from serum previously analyzed for OCPs among 251 cases and 538 controls linked to the wealth of existing study data to address the primary aims: to test whether the risk of endometriosis is associated with urinary levels of 8 phthalate metabolites, to test whether the risk of endometriosis is associated with serum levels of 14 OCPs, or self-report of OCP exposure, and to identify predictors associated with the upper quartile of urinary phthalate metabolite levels, or serum OCP levels, among controls. The secondary aims are to test whether the risk of endometriosis recurrence is associated with 8 urinary phthalate metabolite levels, or serum levels to 14 OCPs and to examine the correlation between serum levels of 14 OCPs and self-report of exposure to 14 OCPs among controls. The proposed project will make an important contribution to the National Institute of Nursing Research's research program to integrate biology and behavior to advance science. The results of this study will address the gap in knowledge about the potential adverse effects of phthalates and OCPs on human health. PUBLIC HEALTH RELEVANCE: This study investigates the relationship between adult exposure to phthalates and organochlorine pesticides in relation to endometriosis, a common female reproductive condition that is associated with infertility and chronic pelvic pain. The findings of this study have the potential for considerable public health importance given the widespread exposure of the US population to phthalates, the environmental persistence of organochlorine pesticides, and the adverse reproductive effects exhibited by these chemicals in female animal studies.